Statine, i.e., 4-amino-3-hydroxy-6-methylheptanoic acid, is an amino acid present in pepstatin, which is known to be an important fragment in certain renin inhibitors. Closely related to statine are certain substituted 4-amino-3-hydroxy-pentanoic acids. These acids are currently of interest in the preparation of renin inhibitors. Two publications concerning these pentanoic acid analogs are: D. H. Rich and E. T. O. Sun, J. Med. Chem. 23, 27 (1980) and J. A. Boger and D. F. Veber, U.S. Pat. No. 4,485,099 (1984), the disclosures of which are hereby incorporated by reference.
The compounds, N-(tert.-butoxycarbonyl)-4(S)-amino-3(S)-hydroxy-5-phenylpentanoic acid (hereafter "S,S-Boc-benztine") and N-(tert.-butoxycarbonyl)-4(S)-amino-3(S)-hydroxy-5-cyclohexanepentanoic acid (hereafter "S,S-Boc-cyclotine") are components of renin inhibitors. The separation of the S,S-isomers from mixtures of diastereomers containing them can be effected by column chromatography of their esters on a small scale. However, a technigue useful for the large scale recovery of these compounds is desirable.
This application is related to U.S. Ser. No. 735,933, filed May 20, 1985, now U.S. Pat. No. 4,650,897, which deals with the separation of certain Boc-statine isomers.